Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Mar;63(3):453-461.
doi: 10.1007/s00125-019-05040-3. Epub 2019 Nov 21.

Sex differences in metabolic regulation and diabetes susceptibility

Blandine Tramunt  1   2 , Sarra Smati  1   3 , Naia Grandgeorge  2 , Françoise Lenfant  1 , Jean-François Arnal  1 , Alexandra Montagner  1 , Pierre Gourdy  4   5
Affiliations
Review

Sex differences in metabolic regulation and diabetes susceptibility

Blandine Tramunt et al. Diabetologia. 2020 Mar.

Abstract

Gender and biological sex impact the pathogenesis of numerous diseases, including metabolic disorders such as diabetes. In most parts of the world, diabetes is more prevalent in men than in women, especially in middle-aged populations. In line with this, considering almost all animal models, males are more likely to develop obesity, insulin resistance and hyperglycaemia than females in response to nutritional challenges. As summarised in this review, it is now obvious that many aspects of energy balance and glucose metabolism are regulated differently in males and females and influence their predisposition to type 2 diabetes. During their reproductive life, women exhibit specificities in energy partitioning as compared with men, with carbohydrate and lipid utilisation as fuel sources that favour energy storage in subcutaneous adipose tissues and preserve them from visceral and ectopic fat accumulation. Insulin sensitivity is higher in women, who are also characterised by higher capacities for insulin secretion and incretin responses than men; although, these sex advantages all disappear when glucose tolerance deteriorates towards diabetes. Clinical and experimental observations evidence the protective actions of endogenous oestrogens, mainly through oestrogen receptor α activation in various tissues, including the brain, the liver, skeletal muscle, adipose tissue and pancreatic beta cells. However, beside sex steroids, underlying mechanisms need to be further investigated, especially the role of sex chromosomes, fetal/neonatal programming and epigenetic modifications. On the path to precision medicine, further deciphering sex-specific traits in energy balance and glucose homeostasis is indeed a priority topic to optimise individual approaches in type 2 diabetes prevention and treatment.

Keywords: Diabetes; Energy balance; Glucose metabolism; Oestrogens; Review; Sex differences.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Main sex dimorphisms in body composition and metabolic homeostasis in humans (premenopausal women vs age-matched men). This figure is available as part of a downloadable slideset
Fig. 2
Fig. 2
Tissue-specific actions of oestrogens on energy balance and metabolic regulation in rodent models. FGF21, fibroblast growth factor 21. This figure is available as part of a downloadable slideset
See this image and copyright information in PMC

References

    1. Rich-Edwards JW, Kaiser UB, Chen GL, Manson JE, Goldstein JM. Sex and gender differences research design for basic, clinical, and population studies: essentials for investigators. Endocr Rev. 2018;39(4):424–439. doi: 10.1210/er.2017-00246. - DOI - PMC - PubMed
    1. Mauvais-Jarvis F, Arnold AP, Reue K. A guide for the design of pre-clinical studies on sex differences in metabolism. Cell Metab. 2017;25(6):1216–1230. doi: 10.1016/j.cmet.2017.04.033. - DOI - PMC - PubMed
    1. Kautzky-Willer A, Harreiter J, Pacini G. Sex and gender differences in risk, pathophysiology and complications of type 2 diabetes mellitus. Endocr Rev. 2016;37(3):278–316. doi: 10.1210/er.2015-1137. - DOI - PMC - PubMed
    1. NCD Risk Factor Collaboration (NCD-RisC) Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants. Lancet. 2016;387(10027):1513–1530. doi: 10.1016/S0140-6736(16)00618-8. - DOI - PMC - PubMed
    1. Peters SAE, Muntner P, Woodward M. Sex differences in the prevalence of, and trends in, cardiovascular risk factors, treatment, and control in the United States, 2001 to 2016. Circulation. 2019;139(8):1025–1035. doi: 10.1161/CIRCULATIONAHA.118.035550. - DOI - PubMed

Publication types